Atherosclerosis 153 2000 147 – 153
Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men
Erkki Ilveskoski
b,c
, Antti Loimaala
a
, Michele F. Mercuri
d
, Terho Lehtima¨ki
b,c,
, Matti Pasanen
a
, Arja Nenonen
a
, Pekka Oja
a
, M. Gene Bond
d
, Timo Koivula
b
, Pekka J. Karhunen
c
, Ilkka Vuori
a
a
UKK Institute for Health Promotion Research, Tampere, Finland
b
Department of Clinical Chemistry, Laboratory of Atherosclerosis Genetics, Tampere Uni6ersity Hospital, P.O. Box
2000
, FIN-
33521
, Tampere, Finland
c
Medical School, Uni6ersity of Tampere, Tampere, Finland
d
The Bowman Gray School of Medicine, Winston-Salem, NC, USA Received 27 April 1999; received in revised form 19 November 1999; accepted 5 January 2000
Abstract
Genetic polymorphism of apolipoprotein E apoE is an important factor in the development of coronary artery disease but the results concerning apoE genotype and carotid artery atherosclerosis remain controversial. We investigated a random sample of
189 Finnish middle aged men mean age 54 years, range 50 – 59 to assess the role of apoE in the process of carotid atherosclerosis. Intima-media thickness IMT of the carotid artery wall was measured at three standardised segments common carotid artery,
bifurcation and internal carotid artery by B-mode ultrasonography. Overall mean IMT value was also calculated. The carriers of E32 n = 20 genotype had significantly lower P B 0.01 total cholesterol and LDL cholesterol concentrations than carriers of
E33 genotype n = 109 or the E4 allele n = 60. ApoE polymorphism was associated with common carotid artery IMT P = 0.034 when adjusted for age and body-mass index model 1. The carriers of E32 had on average 9 95 CI 0.8 – 16,
P = 0.028 lower common carotid IMT values than the carriers of E33. After further adjustment with LDL and HDL cholesterol, systolic blood pressure, lipoprotein a, apolipoprotein B and pack-years of smoking model 2 the association was not statistically
significant. The overall mean IMT varied significantly with apoE genotype P = 0.03 for model 1 and P = 0.07 for model 2, and it was also lowest in the carriers of E32 genotype. This suggests that apoE E32 genotype is a protective factor in the development
of carotid artery atherosclerosis in randomly selected middle-aged men. The favourable effect might be mediated at least partly by the lowering effect of E32 genotype on serum cholesterol. © 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Apolipoprotein E; Polymorphism; Carotid atherosclerosis; Ultrasonics; Intima-media thickness www.elsevier.comlocateatherosclerosis
1. Introduction
Cardiovascular diseases remain important causes of morbidity and mortality in Western countries. Much
attention has been paid to the classic risk factors for atherosclerosis. However, they explain only a part of
the susceptibility, and it would be valuable to find the predisposing genes. One candidate gene is apolipo-
protein E apoE, which is a polymorphic glycoprotein having an important influence on the lipid metabolism
[1 – 3]. The common three isoforms of the protein are designated E2, E3 and E4, and codominant inheritance
leads to six phenotypes E22, E32, E42, E33, E43 and E44 of which E33 is the most common [4].
Several studies in different populations have shown that the carriers of the apoE E4 allele have higher total
cholesterol TC and low density lipoprotein LDL cholesterol values and the E2 in turn is associated with
lower values [2,5 – 9]. Further, the E4 allele is associated with coronary heart disease CHD in patients with
angina pectoris symptoms, and with coronary artery disease CAD in patients with angiographically verified
Corresponding author. Tel.: + 358-3-2474066; fax: + 358-3- 2475554.
E-mail address
:
blteleuta.fi T. Lehtima¨ki. 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 0 2 1 - 9 1 5 0 0 0 0 0 3 8 3 - X
coronary stenosis [5,10 – 12]. Increased incidence of my- ocardial infarction has also been reported in patients
with the E4 allele [13]. On the other hand, there are also studies suggesting that the E2 allele protects from CAD
and from myocardial infarction [5,14,15]. The role of apoE polymorphism has also been studied in stroke but
the results are controversial, and besides the ‘bad allele’ E4, the protective E2 isoform has also been associated
with stroke [16,17].
Age, high systolic blood pressure, cigarette smoking, and high LDL cholesterol concentration all increase the
carotid artery intima-media thickness IMT measured by B-mode ultrasonography [18,19]. Genetics is sug-
gested to determine a large part of the variability of the carotid IMT in healthy people [20]. Further, it has been
shown that there is also an association between CAD and carotid artery disease determined by measuring the
carotid artery IMT [21]. Since apoE polymorphism has an effect on serum LDL cholesterol concentration and
on the risk for CAD, it may also play a role in the development of atherosclerosis in the carotid artery.
There are only a few studies concerning the relationship between carotid atherosclerosis and apoE, and both
E32 genotype and the E4 allele have been associated with carotid artery intima-media thickness IMT mea-
sured by ultrasonography [22,23]. However, a lack of association of apoE polymorphism with carotid IMT
has also been reported [24]. The possible protective effect of the E2 allele, as it has on the development of
CAD, has not been studied in detail previously.
To clarify the association between apoE polymor- phism and carotid atherosclerosis we examined a ran-
dom sample of 189 middle aged men who underwent carotid artery ultrasonography.
2. Materials and methods
